Gassen, Nils C.; Niemeyer, Daniela; Muth, Doreen; Corman, Victor M.; Martinelli, Silvia; Gassen, Alwine; Hafner, Kathrin; Papies, Jan; Moesbauer, Kirstin; Zellner, Andreas; Zannas, Anthony S.; Herrmann, Alexander; Holsboer, Florian; Brack-Werner, Ruth; Boshart, Michael; Müller-Myhsok, Bertram; Drosten, Christian; Müller, Marcel A.; Rein, Theo (2019): SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. In: Nature Communications, Vol. 10, 5770 |
| Creative Commons Attribution 2MB |
Abstract
Autophagy is an essential cellular process affecting virus infections and other diseases and Beclinl (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.
Item Type: | Journal article |
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Faculties: | Biology > Department Biology I |
Subjects: | 500 Science > 570 Life sciences; biology |
URN: | urn:nbn:de:bvb:19-epub-83665-8 |
ISSN: | 2041-1723 |
Language: | English |
ID Code: | 83665 |
Deposited On: | 15. Dec 2021 15:08 |
Last Modified: | 27. Jan 2022 06:28 |
- BASE
- Gassen, Nils C.
- Niemeyer, Daniela
- Muth, Doreen
- Corman, Victor M.
- Martinelli, Silvia
- Gassen, Alwine
- Hafner, Kathrin
- Papies, Jan
- Moesbauer, Kirstin
- Zellner, Andreas
- Zannas, Anthony S.
- Herrmann, Alexander
- Holsboer, Florian
- Brack-Werner, Ruth
- Boshart, Michael
- Müller-Myhsok, Bertram
- Drosten, Christian
- Müller, Marcel A.
- Rein, Theo
- Google Scholar
- Gassen, Nils C.
- Niemeyer, Daniela
- Muth, Doreen
- Corman, Victor M.
- Martinelli, Silvia
- Gassen, Alwine
- Hafner, Kathrin
- Papies, Jan
- Moesbauer, Kirstin
- Zellner, Andreas
- Zannas, Anthony S.
- Herrmann, Alexander
- Holsboer, Florian
- Brack-Werner, Ruth
- Boshart, Michael
- Müller-Myhsok, Bertram
- Drosten, Christian
- Müller, Marcel A.
- Rein, Theo